β_2-integrin, LFA-1-mediated p125^<FAK> activation

概要

論文の詳細を見る
Accumulation of T cells at inflammatory sites is one of the characteristic features of infection, autoimmune and chronic inflammatory diseases. Optimal activation of T cells requires the binding of the MHC/Ag complex with T cell receptor, as well as a secondary signal initiated by costimulatory molecules such as CD2, CD28 or integrins. Focal adhesion kinase, pp125^<FAK> (FAK) has been previously shown to be localized in focal adhesions in fibroblasts and to be involved in integrin-mediated cellular activation. Although signaling through β_1- or β_3-integrins induces tyrosine phosphorylation of FAK, there has been no evidence that activation of T cells through the β_2-integrin, lymphocyte functionassociated antigen (LFA) -1, involves FAK. We report here that crosslinking of LFA-1 induces tyrosine phosphorylation of FAK in PHA-activated T cells. Moreover, cocrosslinking with anti-LFA-1 monoclonal antibody (mAb) and suboptimal concentration of anti-CD3 mAb markedly increases tyrosine phosphorylation of FAK in an antibody-concentration and time-dependent manner compared with stimulation through CD3 alone. Furthermore this increased phosphorylation correlates well with the enhanced proliferation of PHA-activated T cells. Results indicate that signals mediated by LFA-1 can regulate FAK, suggesting that LFA-1-mediated T cell costimulation may be involved in T cell activation at least partially through FAK.
大阪歯科学会の論文